ADAM17 is an essential attachment factor for classical swine fever virus

PLoS Pathog. 2021 Mar 8;17(3):e1009393. doi: 10.1371/journal.ppat.1009393. eCollection 2021 Mar.

Abstract

Classical swine fever virus (CSFV) is an important pathogen in the swine industry. Virion attachment is mediated by envelope proteins Erns and E2, and E2 is indispensable. Using a pull-down assay with soluble E2 as the bait, we demonstrated that ADAM17, a disintegrin and metalloproteinase 17, is essential for CSFV entry. Loss of ADAM17 in a permissive cell line eliminated E2 binding and viral entry, but compensation with pig ADAM17 cDNA completely rescued these phenotypes. Similarly, ADAM17 silencing in primary porcine fibroblasts significantly impaired virus infection. In addition, human and mouse ADAM17, which is highly homologous to pig ADAM17, also mediated CSFV entry. The metalloproteinase domain of ADAM17 bound directly to E2 protein in a zinc-dependent manner. A surface exposed region within this domain was mapped and shown to be critical for CSFV entry. These findings clearly demonstrate that ADAM17 serves as an essential attachment factor for CSFV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM17 Protein / metabolism*
  • Animals
  • Classical Swine Fever
  • Classical Swine Fever Virus / metabolism*
  • Classical Swine Fever Virus / pathogenicity
  • Humans
  • Receptors, Virus / metabolism*
  • Swine
  • Viral Envelope Proteins / metabolism*
  • Virus Internalization*

Substances

  • Receptors, Virus
  • Viral Envelope Proteins
  • ADAM17 Protein

Grant support

A.Z. received all the grants. This project was funded by the National Key Plan for Scientific Research and Development of China (2016YFD0500303), the National Science and Technology Major Project (2018ZX10101004) and National Natural Science Foundation of China, General Program (81871687). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.